NDLI: Subtoxic Concentrations of Hepatotoxic Drugs Lead to Kupffer Cell Activation in a Human In Vitro Liver Model: An Approach to Study DILI

Content Provider	PubMed Central
Author	Kegel, Victoria Pfeiffer, Elisa Burkhardt, Britta Liu, Jia L. Zeilinger, Katrin Nüssler, Andreas K. Seehofer, Daniel Damm, Georg
Copyright Year	2015
Abstract	Drug induced liver injury (DILI) is an idiosyncratic adverse drug reaction leading to severe liver damage. Kupffer cells (KC) sense hepatic tissue stress/damage and therefore could be a tool for the estimation of consequent effects associated with DILI. Aim of the present study was to establish a human in vitro liver model for the investigation of immune-mediated signaling in the pathogenesis of DILI. Hepatocytes and KC were isolated from human liver specimens. The isolated KC yield was 1.2 ± 0.9 × 106 cells/g liver tissue with a purity of >80%. KC activation was investigated by the measurement of reactive oxygen intermediates (ROI, DCF assay) and cell activity (XTT assay). The initial KC activation levels showed broad donor variability. Additional activation of KC using supernatants of hepatocytes treated with hepatotoxic drugs increased KC activity and led to donor-dependent changes in the formation of ROI compared to KC incubated with supernatants from untreated hepatocytes. Additionally, a compound- and donor-dependent increase in proinflammatory cytokines or in anti-inflammatory cytokines was detected. In conclusion, KC related immune signaling in hepatotoxicity was successfully determined in a newly established in vitro liver model. KC were able to detect hepatocyte stress/damage and to transmit a donor- and compound-dependent immune response via cytokine production.
Related Links	http://dx.doi.org/10.1155/2015/640631
Starting Page	640631
File Format	PDF
ISSN	14661861
e-ISSN	14661861
Journal	Mediators of Inflammation
Volume Number	2015
Language	English
Publisher	Hindawi Publishing Corporation
Publisher Date	2015-01-01
Access Restriction	Open
Rights Holder	Hindawi Publishing Corporation
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Immunology

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